This application is part of a two-site collaborative renewal grant with an identical (except for budget/personnel) application submitted concurrently by Dr. Lyn Y. Abramson (University of Wisconsin) under the same title. Although important biological work has been conducted on Bipolar (Bi) disorder, less work has examined psychosocial factors in the onset, course, and progression of this disorder. Thus, in this proposal, theories implicating the Behavioral Approach System (BAS) in Bi Spectrum disorders are integrated with work on - psychosocial factors these conditions to provide a theoretically consistent and methodologically rigorous biopsychosocial framework to guide a prospective study of the course and progression of Bi disturbance. In the current grant, a unique sample of 206 Ss initially exhibiting milder Bi disturbance (Cyclothymia [Cyc] and Bi II), many of whom now are progressing to a more severe course, and 214 demographically-matched Normal controls (Nors) with no lifetime history of any psychopathology has been assembled and followed prospectively for an average of 21 months with independent and blind self-report and interview assessments (every 16 weeks) of life events, cognition, and psychiatric status/symptoms. At the outset of the proposed continued follow-up of this sample, laboratory assessments of BAS profiles, both in the resting state and in response to BAS-relevant cues, using psychophysiological (EEG assessments of left frontal cortical activity), behavioral (task persistence vs. helplessness), and subjective affect (euphoria, anger/irritability, depression) indices will be conducted to test the hypothesis that Bi Ss exhibit dysregulated BAS activity compared to Nor Ss. Moreover, life events, with a focus on those that are BAS-relevant, laboratory BAS profile, and cognitive vulnerability will be examined in the prediction of Hypomania/Mania and Depression symptoms and episodes among Bi and Nor Ss in the continued 3-year prospective follow-up. Finally, these same factors will be examined to predict general worsening of course and progression to Bi II and Bi I status among the Bi Ss.